Magnesium is one of the most essential minerals for humans to consume. The intake of magnesium is down due to the rise in popularity of processed foods. Spinach, pumpkin seeds and halibut are all excellent sources of magnesium. The FDA has approved the use of Epsom salt (magnesium sulfate) as a laxative. It can also be used to help cure migraines, diabetes, hypertension, PMS, and leg cramps. It can be found in capsule, tablet, cream and solution form.
Magnesium is an essential mineral. Average daily intakes of dietary magnesium have declined in recent years due to processing of food. The average daily intake has been estimated to be approximately 300 to 360 mg. Some experts suggest an increased daily intake of 440 to 490 mg, especially if the patient is pregnant, taking potent loop diuretics, or rarely eating a well-balanced meal containing green leafy vegetables, legumes, nuts, or animal protein (Whang et al, 1994).
Magnesium sulfate is used for replacement therapy for hypomagnesemia; in total parenteral nutrition to correct or prevent deficiencies; to control or prevent seizures in preeclampsia; and in the oral form as a cathartic. Magnesium may also be effective in treating certain cardiac arrhythmias, in asthma when unresponsive to other treatments, during alcohol withdrawal, and for ischemic heart disease.
Patients with congestive heart failure often take medications that may deplete magnesium to the extent that arrhythmias occur or are worsened. Magnesium therapy has inconsistent effects on hypertension, but should be considered in those at risk of deficiency, including women and patients taking magnesium-depleting medications.
The scope of this discussion will be limited to the oral formulations.
Actions & Pharmacology
Magnesium is said to exhibit anti-osteoporotic activity; anti-arrhythmic, antihypertensive, glucose regulatory, bronchodilator. It is an electrolyte, a nutrient, and a mineral.
Magnesium is important as a cofactor in many enzymatic reactions in the body (Gilman et al, 1990; Havel et al,1989). There are at least 300 enzymes that are dependent upon magnesium for normal functioning. Actions on lipoprotein lipase have been found to be important in reducing serum cholesterol (Davis et al, 1984). Magnesium is necessary for maintaining serum potassium and calcium levels due to its effect on the renal tubule (Rasmussen et al, 1988).
In the heart magnesium acts as a calcium channel blocker. It also activates sodium-potassium ATPase in the cell membrane to promote resting polarization and reduce arrhythmias (Shattock et al, 1987).
According to a recent meta-analysis, supplementation with oral magnesium (Mg) may be effective in reducing plasma glucose levels, although it was not shown to produce significant reductions in levels of glycated hemoglobin (HbA1C). Nine randomized, double-blind, controlled studies including 370 patients with type 2 diabetes were identified for inclusion in the review. The median dose of supplemental Mg was 360 mg/day in the groups receiving active treatment. Although no significant differences were observed between groups in post-intervention HbA1c after a median term of 12 weeks, the weighted mean post-intervention fasting glucose was significantly lower in the treatment groups vs the control groups (–0.56 mmol/l; p for heterogeneity = 0.02). The reviewers conceded that since most of the studies cited in the meta-analysis were short-term trials, the results provided may underestimate the actual effect of magnesium supplementation on long-term glycemic control. Additional large-scale trials of longer duration are therefore warranted. (Song et al, 2006)
High doses of magnesium significantly reduced plasma fructosamine in type 2 diabetics, but did not affect fasting glucose or HbA1c; half of that dose was without effect on any of those parameters. In a randomized, double-blind trial, 128 type 2 diabetics with poor glycemic control while being treated by diet or diet plus hypoglycemic drugs were given placebo, magnesium (as MgO) 20.7 mmol/day, or Mg 41.4 mmol/day for 30 days. Before supplementation, 31% of subjects had low intramononuclear Mg levels, compared to a control group of blood donors. In the 29 patients with peripheral neuropathy, intracellular Mg was significantly lower (p<0.05) than in those without it. After 30 days, no change in plasma or intracellular Mg or improvement in glycemic control was evident in the placebo group or the lower dose Mg group. In the higher dose Mg group, fructosamine fell from 4.1 to 3.8 mmol (p<0.05) and urinary Mg increased. There were no significant changes in plasma or intracellular Mg, HbA1, or fasting glucose (Lima et al, 1998).
Three months of magnesium supplementation 15 mmol/day did not improve glycemic control in insulin-requiring type 2 diabetics. Fifty patients who were not necessarily hypomagnesemic but had used insulin for at least 6 months were randomized to receive magnesium as Mg-asparate-HCl or placebo. Plasma Mg concentration and urinary Mg excretion were significantly higher in the Mg group than in the placebo group after 3 months' treatment (p<0.05 and p=0.004, respectively), but there were no differences between the groups in plasma glucose, HbA1c, plasma cholesterol, or plasma triglycerides (de Valk et al, 1998).
A randomized, double-blind, cross-over study was conducted to assess effects of magnesium in noninsulin-dependent diabetes. Patients with type 2 diabetes (n=9) treated by diet only received either 15.8 mmol Mg daily or a placebo for 4 weeks. Serum levels were measured after each treatment period. Increased plasma Mg levels, total body glucose disposal (p<0.005) and glucose oxidation (p<0.01) were observed with Mg supplementation (Paolisso et al, 1994).
A randomized, double-blind, placebo-controlled study was done to assess effects of magnesium treatment in type 2 diabetes. Patients with type 2 diabetes (n=40) were given 30 mmol Mg daily or a placebo for 3 months. Serum and urine measurements were done at the beginning, and at 2 and 3 months. Plasma Mg levels increased after the 3-month treatment but declined to pretreatment levels after 6 months (Eibl et al, 1995).
Uncertainty remains as to the clinical utility of supplemental magnesium for controlling blood pressure (BP). A recent Cochrane review of the effectiveness of magnesium supplementation for the management of primary hypertension in adults identified 12 randomized, controlled trials (total n=545) for inclusion. Combined trial results from hypertensive subjects receiving magnesium showed no significant reductions in systolic BP as compared to controls. Although small, significant reductions in diastolic BP were noted in those receiving magnesium, the reduction was small (2.2 mm Hg) and may not last beyond 26 weeks. Lacking a clear, sustained effect on BP, the reviewers concluded that evidence from the trials was not strong enough to establish an association between magnesium supplementation and BP reduction. Additionally, they state that the reduction in diastolic BP may be the result of bias. Larger, randomized, double-blind, placebo-controlled studies with longer follow-up are needed (Dickinson et al, 2007).
An earlier meta-analysis of randomized studies investigating the effects of magnesium supplementation on BP showed a dose-dependent effect. Twenty trials (total n=1,220), including 14 trials with hypertensive subjects, met inclusion criteria, including randomization, use of a control group, magnesium as the sole treatment, and sufficient data to calculate the difference in BP change between the active and control treatments. The dose of magnesium varied from 10 to 40 mmol/day. For every 10-mmol increase in daily Mg intake, there was a reduction in systolic BP of 4.3 mm Hg (p<0.001) and in diastolic BP 2.3 mm Hg (p=0.09). This result still remains to be confirmed by adequately powered trials (Jee et al, 2002).
However, in the Cochrane review by Dickinson noted above, several limitations to the meta-analysis by Jee are noted, including the fact that it was not restricted to trials involving hypertensive populations, nor did it exclude trials in which subjects received various antihypertensive medications during the trials. Some studies included in the meta-analysis by Jee had less than 8 weeks of follow-up, hindering observations on sustained effects. Nevertheless, both the meta-analysis by Jee and the Cochrane review by Dickinson are consistent in one regard: the finding that overall, magnesium supplementation had little effect on the BP of subjects with hypertension.
A recent review of natural or alternative treatments for prevention of migraine cited one randomized, double-blind, placebo-controlled trial that showed no significant superiority of magnesium over placebo. In this study of children aged 3 to 17 years, active treatment consisted of daily magnesium oxide 9 mg/kg in three divided doses. Among the subjects completing the study (about 75%), a significant downward trend in headache days was observed in the active treatment (magnesium) group vs placebo; however, the lack of any difference in the slope of treatment trends precluded the authors from making any claims of significant superiority for magnesium(Evans and Taylor, 2006).
Oral magnesium was effective in reducing the frequency of migraine headaches in an earlier 12-week, multicenter, placebo-controlled, double-blind study. Of 81 patients, 43 were administered magnesium 600 mg (24 mmol) (trimagnesium dicitrate) every day for 12 weeks and 38 were given placebo. After 9 weeks of therapy, the average frequency of attacks was reduced in the Mg-treated group compared with the placebo-treated group (41.6% vs 15.8%, p=0.03) and compared with baseline (p=0.04). The number of days with migraine was also reduced in the Mg group (52.3%) compared with placebo (19.5%) (p=0.03). The average duration of attack, pain intensity, and amount of acute medication required per person were also reduced in the treatment group compared with placebo; these differences were not statistically significant. The major adverse events reported consisted of diarrhea and gastric irritation (Peikert et al, 1996).
A similarly designed study showed no difference between magnesium and placebo treatment in prevention of migraine. Sixty-nine patients with confirmed history of migraine without aura were randomly assigned to a 12-week treatment of either 20 mmol Mg-L-aspartate-hydrochloride twice daily (n=35) or an identical-appearing placebo (n=34). Responders were identified as those with a 50% reduction in the duration of migraine in hours or in the intensity of migraine at the end of the third month of treatment in comparison to baseline values. There were 10 responders in each group; specifically, the responder rate was 28.6% in the group receiving magnesium and 29.4% in subjects receiving placebo. There was no difference between groups in the absolute number of migraine days or the number of migraine attacks during the study. Although physicians' assessments of efficacy were nearly the same for the two treatments, 33% of the magnesium group and only 11% of the placebo group regarded the study medication to be superior to previously used migraine prophylactics. The authors mentioned that some patients started using sumatriptan to treat migraine attacks; this may have biased outcomes. They recommended that future studies provide a standardized scheme for treatment of attacks during the study (Pfaffenrath et al, 1996).
Magnesium supplementation was associated with accrual of bone mass in one study. A small cohort of healthy 8- to 14-year-old girls with suboptimal intakes of dietary magnesium was enrolled in this randomized, placebo-controlled study. Girls were assigned to 12 months of treatment with either 300 mg/day supplemental magnesium (n=23) or placebo (n=27). By treatment end, significantly increased accrual in integrated hip bone mineral content (BMC) was observed in the magnesium-supplemented group compared with placebo (p=0.05), an approximate 3% increase compared with baseline measurements. A slightly greater, though not statistically significant, mean incremental gain in spinal BMC was noted in the magnesium-supplemented group as well (Carpenter et al, 2006).
A cross-sectional analysis was conducted to assess dietary components in bone mineral density (BMD). Cohorts in a heart study were analyzed for changes in BMD and dietary intake. Baseline BMDs were obtained in individuals (n=628) and dietary intake was assessed by questionnaires. Changes in a 4-year period were analyzed in BMD. Greater magnesium intake was associated with a lesser decline in BMD (Tucker et al, 1999).
Patients with gluten-sensitive enteropathy (sprue) and associated osteoporosis showed increases in BMD after 2 years of magnesium therapy. Five patients took magnesium 504 to 576 mg daily, as either Mg chloride or Mg lactate, for 2 years. Erythrocyte magnesium concentrations rose from 137 microM at baseline to 193 microM at 2 years (p<0.02) (normal 202 ± 6 microM). Serum parathyroid hormone rose from 37 to 63 pg/mL at the 3-month point (p<0.04) (normal 10 to 55 pg/mL). BMD increased at all sites measured–significantly, so at both the femoral neck and proximal femur (p<0.04). Increases in BMD correlated well (r=0.95) with the rise in erythrocyte magnesium, which had been significantly below normal at the start of study (Rude & Olerich, 1996).
Indications & Usage
Approved by the FDA:
- Magnesium sulfate (Epsom salt) is approved as a laxative for the temporary relief of constipation.
Magnesium is used for migraine, bone resorption, diabetes, hypertension, arrhythmias, PMS, nephrolithiasis, spasms, and leg cramps during pregnancy.
Magnesium is not to be used in the presence of heart block, severe renal disease, or toxemia in the 2 hours preceding delivery.
Precautions & Adverse Reactions
Side effects include blurred vision, photophobia, diarrhea, hypermagnesemia, hypotension, increased bleeding times, neuromuscular blockade (in higher doses), and vasodilation.
Administration of magnesium, especially in renally impaired patients, may lead to loss of deep tendon reflexes, hypotension, confusion, respiratory paralysis, cardiac arrhythmias, or cardiac arrest. Increased bleeding time has been reported. Monitor to avoid magnesium toxicity.
Concurrent use of magnesium-containing products and dairy foods may result in altered serum calcium concentrations.
Rickets in the newborn may result from prolonged magnesium sulfate administration in the second trimester of pregnancy.
Concomitant use with magnesium may precipitate QT prolongation. Clinical Management: Caution should be used when prescribing concomitant drugs known to induce hypokalemia or hypomagnesemia, such as laxatives, as they may precipitate QT prolongation and interact with levomethadyl.
Concomitant use with magnesium may precipitate neuromuscular weakness and possibly paralysis. Clinical Management: Monitor patients for respiratory dysfunction and apnea. If neuromuscular blockade occurs, discontinue the aminoglycoside and change antibiotic therapy. Patients receiving large cumulative doses of aminoglycosides should have serum calcium, magnesium, potassium, and creatinine monitored.
Calcium channel blockers
Concomitant use with magnesium may enhance hypotensive effects. Clinical Management: Monitor blood pressure closely when adding or deleting calcium channel blockers in patients receiving magnesium
Concurrent use of doxercalciferol and magnesium may result in hypermagnesemia. Clinical Management: Avoid concomitant use.
Concomitant use with magnesium may decrease absorption and effectiveness. Clinical Management: Fluoroquinolones should be administered at least 4 hours before magnesium or any product containing magnesium.
Concomitant use with magnesium may cause bradycardia and reduced cardiac output. Clinical Management: Myocardial function should be monitored when using concomitant magnesium sulfate and labetalol.
Concomitant use with magnesium may enhance neuromuscular blocking effects. Clinical Management: The dose of neuromuscular blocker may need to be adjusted downward in patients receiving large doses of magnesium salts administered for toxemia of pregnancy.
Hypermagnesemia from magnesium administration is most commonly seen in patients with renal insufficiency. Hypermagnesemia presents as muscle weakness, electrocardiogram changes, sedation, hypotension, and confusion. These symptoms will progress to absent deep-tendon reflexes, respiratory paralysis, and heart block (Gilman et al, 1990).
Respiratory paralysis occurs at 12 to 15 mEq/L, while concentrations greater than 15 mEq/L result in cardiac conduction abnormalities and cardiac arrest (Gilman et al, 1990).
Mode of Administration
Intramuscular, intravenous, oral, topical
Capsule, cream, solution, tablet
The following chart lists the Recommended Dietary Allowance (RDA) for magnesium:
|0 to 6 months||30 mg/day||30 mg/day|
|7 to 12 months||75 mg/day||75 mg/day|
|1 to 3 years||80 mg/day||80 mg/day|
|4 to 8 years||130 mg/day||130 mg/day|
|9 to 13 years||240 mg/day||240 mg/day||400 mg/day||400 mg/day|
|14 to 18 years||410 mg/day||360 mg/day||400 mg/day||360 mg/day|
|19 to 30 years||400 mg/day||310 mg/day||350 mg/day||310 mg/day|
|31+ years||420 mg/day||320 mg/day||360 mg/day||320 mg/day|
Abdominal and Perineal Incision Wound Healing (magnesium hydroxide ointment, topical): apply twice daily along with zinc chloride spray for 7 days.
Congestive Heart Failure (enteric-coated magnesium chloride): 3,204 mg/d in divided doses (equal to 15.8 mmol elemental Mg).
Dentine Hypersensitivity: 4% Magnesium sulfate solution applied by iontophoresis.
Detrusor Instability (magnesium hydroxide): 350 mg for 4 weeks; double after 2 weeks if there is an unsatisfactory response.
Diabetes Mellitus Type 2: 15.8 to 41.4 mmol/d.
Dietary Supplement: 54 to 483 mg daily in divided doses.
Dyslipidemia (enteric-coated magnesium chloride): a mean dose of 17.92 mmol for a mean duration of 118 days; OR magnesium oxide, 15 mmol/d for 3 months.
Hypertension: 360 to 600 mg/d.
Migraine Prophylaxis: 360 to 600 mg/d.
Mitral Valve Prolapse (magnesium carbonate capsules): During the first week of treatment, 21 mmol/d is used; then 14 mmol/d is used during the second to fifth weeks.
Nephrolithiasis Prophylaxis (magnesium hydroxide): 400 to 500 mg/d.
Osteoporosis: 250 mg taken at bedtime on an empty stomach, increased to 250 mg three times daily for 6 months, followed by 250 mg daily for 18 months.
Premenstrual Syndrome: 200 to 360 mg/d.
Deficiency: The oral dose of magnesium sulfate to treat hypomagnesemia in children is 100 to 200 mg/kg four times daily.
Dietary Supplement: 3 to 6 mg/kg body weight per day in divided doses 3 to 4 times daily, up to a maximum of 400 mg daily.
Laxative: The recommended dose of magnesium citrate for children 2 to 5 years of age is 2.7 to 6.25 g daily as a single or divided dose. For children 6 to 11 years of age, the dose is 5.5 to 12.5 g daily in single or divided doses.